Effect of Unfractionated and Low-Molecular-Weight Heparin on OPG, sRANKL, and von Willebrand Factor Concentrations During Hemodialysis

Klejna, Katarzyna; Naumnik, Beata; Koc-Żórawska, Ewa; Myśliwiec, Michał

doi:10.1177/1076029612463424

Cited by 8 publications

(9 citation statements)

References 34 publications

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“…Although our results do not support the assumption that heparin could alter the production of OPG and RANKL, in clinical studies of hemodialysis patients [ 31 , 32 ] and healthy students [ 30 ], plasma levels of OPG and soluble RANKL were influenced by treatment with both heparin and low molecular weight heparin. There are two possible explanations for these inconsistent results.…”

Section: Discussioncontrasting

confidence: 99%

Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity

Lü

Chen

et al. 2016

IJMS

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Heparin has been proven to enhance bone resorption and induce bone loss. Since osteoclasts play a pivotal role in bone resorption, the effect of heparin on osteoclastogenesis needs to be clarified. Since osteocytes are the key modulator during osteoclastogenesis, we evaluated heparin’s effect on osteoclastogenesis in vitro by co-culturing an osteocyte cell line (MLO-Y4) and pre-osteoclasts (RAW264.7). In this co-culture system, heparin enhanced osteoclastogenesis and osteoclastic bone resorption while having no influence on the production of RANKL (receptor activator of NFκB ligand), M-CSF (macrophage colony-stimulating factor), and OPG (osteoprotegerin), which are three main regulatory factors derived from osteocytes. According to previous studies, heparin could bind specifically to OPG and inhibit its activity, so we hypothesized that this might be a possible mechanism of heparin activity. To test this hypothesis, osteoclastogenesis was induced using recombinant RANKL or MLO-Y4 supernatant. We found that heparin has no effect on RANKL-induced osteoclastogenesis (contains no OPG). However, after incubation with OPG, the capacity of MLO-Y4 supernatant for supporting osteoclast formation was increased. This effect disappeared after OPG was neutralized and reappeared after OPG was replenished. These results strongly suggest that heparin promotes osteocyte-modulated osteoclastogenesis in vitro, at least partially, through inhibiting OPG activity.

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Section: Discussioncontrasting

confidence: 99%

Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity

Lü

Chen

et al. 2016

IJMS

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“…All the non-English articles were translated but did not meet criteria. Five studies were with a randomized cross-over design [16, 22, 24, 27, 29], nine were non-randomized cross-over [13–15, 17, 19–21, 25, 28] and three parallel design with randomization [18, 23, 26]. Two studies were excluded from the review since they reported the same results as studies included in the present review.…”

Section: Resultsmentioning

confidence: 99%

“…The OPG/RANKL system is involved in bone metabolism. No significant difference between LMWH and UFH (Additional file 2: Table S3) was found [16, 29]. Lai et al [20] measured the bone densitometry with dual energy X-ray and observed an increase of bone mass density (BMD) in ward’s triangle by 0.75% after switching to LMWH.…”

Section: Resultsmentioning

confidence: 99%

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Safety of low-molecular-weight heparin compared to unfractionated heparin in hemodialysis: a systematic review and meta-analysis

et al. 2017

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BackgroundLow molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation.MethodsWe used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables.ResultsSeventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26–2.22). The WMD calculated for total cholesterol was −28.70 mg/dl (95% CI -51.43 to −5.98), a WMD for triglycerides of −55.57 mg/dl (95% CI -94.49 to −16.66) was estimated, and finally LDL-cholesterol had a WMD of −14.88 mg/dl (95% CI -36.27 to 6.51).ConclusionsLMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0596-4) contains supplementary material, which is available to authorized users.

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“…First, most high‐risk individuals received (multi‐)drug treatment. It has been demonstrated that in vivo treatment with antidiabetic medication,43, 44, 45, 46 statins,47, 48 heparins,49, 50 or glucocorticoids51 and in vitro treatment with irbesartan52 or different immunosuppressive therapies53 affect circulating osteoprotegerin levels. Second, circulating osteoprotegerin levels differ in people with preexisting diseases.…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Tschiderer

Klingenschmid

Nagrani

et al. 2018

JAHA

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BackgroundOsteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (CVD) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear.Methods and ResultsThree independent reviewers systematically searched PubMed, EMBASE, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066 CVD events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias (P value from Egger's test=0.013). Correction for publication bias using the trim‐and‐fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03–1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow‐up.ConclusionsIn populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.

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Effect of Unfractionated and Low-Molecular-Weight Heparin on OPG, sRANKL, and von Willebrand Factor Concentrations During Hemodialysis

Abstract: Impact of heparin on endothelial cells and simultaneously on OPG/RANK/RANKL axis reinforces the presumption of the pathophysiological linkage between bone mineralization and endothelial dysfunction in end-stage renal disease.

Cited by 8 publications

References 34 publications

Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity

Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity

Safety of low-molecular-weight heparin compared to unfractionated heparin in hemodialysis: a systematic review and meta-analysis

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

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